Guiding antiviral cell therapy approaches with an online resource of clinically scored epitopes, T cell receptors and B cell receptors

Introduction: The clinical application of cell-based immunotherapies is a rapidly emerging field, and recent advances in gene therapy have opened up a new era of innovative treatment approaches. Introducing a specific T cell receptor (TCR) against viral epitopes or chimeric antigen receptor (CAR) into T cells and effector cells allows reprogramming of their specificity and utilization for advanced therapeutic applications in infectious diseases and virus-induced malignancies. Many technologies have been developed to genetically engineer T cells, and existing databases in silico predict or describe identified viral epitopes, TCRs or B-cell receptors (BCRs). However, their therapeutic application is still hampered by limited knowledge on their clinical impact. Methods: An open-access online resource was developed integrating a data-mining algorithm scoring the Epitopes, TCRs, and BCRs (ETB database) according to clinical evidence. Results: We hereby present a new level of clinical evidence-based knowledge transfer for selecting individual protective TCRs or BCRs for therapeutic application. The database is publicly available at https://app.bitcare.de/epitopeFrontend/. Conclusion: Redirecting T-cell specificity by genetic engineering using clinically protective TCR or chimeric antigen receptor sequences will not only bring significant progress to the field of adoptive T cell therapies (ACT), but also lay the groundwork for broader applications such as off-the-shelf approaches.